Production of esters of hydroxycylohexanones



' and certain new compounds of this series.

Patented Oct. 12, 1943 PRODUCTION or ESTERS or .mmaoxv- CYLOHEXANONES Lucas P. Kyrides, Webster Groves, Mo., assignor to Monsanto Chemical Company, St. Louis; Mo., a corporation of Delaware No Drawing. Original application June 26, 1940,

SerialNo. 342,443.- Divided and this application April 24, 1941, Serial No. 399,108

11 Glaims.

The present invention relates to a new method of preparing esters of hydroxycyclohexanones The invention also relates to plastic compositions of matter which contain plastic substances embodying a plurality of COC linkages and reiers particularly to a new class of softening or plasticizing compositions for useas camphor substi tutes for such plastic compositions, specifically to esters of hydroxycyclohexanones.

This application is a divisional of my prior application, Serial Number 342,443, filed June 26, 1940, in which plastic compositions containing the compounds referred to-herein areclaimed specifically.

The principal object of the invention is to provide improved softening or plasticizing compounds for use in plastic compositions embodying a plurality of COC linkages, particularly cellulose derivatives, for example, cellulose esters and ethers such as cellulose acetate, cellulose nihas also been named 2-acetoxycyclohexane-lone and could be named, according to various systems of nomenclature, as 1,2-cyclohexanolone acetate, acetate of adipoin, or simply o-cyclohexanonyl acetate, none of which names is sufficiently suggestive, however, oila compound cor- 7 responding to a keto-cyclohexanol ester in which trate and ethyl cellulose, and polyvinyl acetal resins, Another object of the invention is to 9 provide a method of preparing such plasticizing of hydroxycyclohexanones are compatible to a remarkable extent with polyvinyl acetal resins and cellulose derivatives such as cellulose acetate and cellulose nitrate and that the plastic compositions resulting from such admixture are characterized by excellent stability to light, good flexibility, high tensile strength and fair elongation. I

The acetate of Z-hydroxycyclohexanone of the formula is an example of an ester of a hydroxycyclohexanone that is suitable for use according to my invention. This compound was first described by Bergmann and Gurth, in Annalen, 1926, vol. 448, page 71, as melting at 41 to 42 C. and boiling at 118 at 12 mm. The compound the carbinol group has been esterified by an acid. l'nroughout this specification, therefore, the compounds will be referred to as esters of 'a hydroxycyclohexanone and it is to be understood tnat the carboxyl group has been substituted in the. cyclohexanone in a manner corresponding to esterification of the hydroxyl group or the hydroxycyclohexanone by an acid, although this is not actually the method by which I meter to produce the compounds. 1

The benzoate of 2-hydroxycyclohexanone is also known and was described by Kotz et al., in Annalen, 1913, vol. 400, page 63,.by Bergmann and Gurth, in Annalen 1926-, vol. 448, page '12 and by Wilson and Read in Journal of the Chemical Society (London), 1935, page 1273, although its melting point was given as 1'22 to 123 C., 87 0., and to 86 C., by the respective investigators.

The esters for use in my invention may be hydroxycyclohexanone esters of simple monocarboxylic aliphatic acids such as formic, acetic, propionic, butyric, valeric (pentanoic), caproic (hexanoic) heptanoic, octanoic and the like, including isomers and higher homologuesthereoi', monocarboxylic aromatic acids such as benzoic, toluic, and the like, their homologues and isomers, as well as esters of polycarboxylic acids containing one free unesterified carboxyl group such as (CzHsOCHzCOOH) monoethyldiglycolic acid (czrnooo-crn-o-crn-ooon) and the like. In general, any acid corresponding to a carboxyl-substituted hydrocarbon or other which may have as optional substituents, chlorine, hydrocarbon radicals or carboxyl radicals esterified by alcohols, ether alcohols or ketoalcohols, may be used. One or more such acid radicals may be substituted in the cyclohexanone nucleus. The hydroxycyclohexanone from which the compounds can be considered to be derived may be 2-hydroxycyclohexanone, 3-hydroxycyclohexanone, 4-hydroxycyclohexanone,polyhydroxycyclohexanones and homologues thereof, although, because of ease of preparation, the monoesters of Z-hydroxycyclohexanone are preferred. In general, the esters of hydroxycyclohexanones for use according to this invention are cyclohexanones in which a hydrogen atom of one or more of the methylene groups is substituted by the radical -OOCX, in which X corresponds to hydrogen (H), a hydrocarbon (R), chlorinated hydrocarbon (RC1), alkoxy-substituted hydrocarbon (ROR), esterified carboxyl-substituted hydrocarbon (-RCOOR) or esterified carboxyl and alkoxy-substituted hydrocarbon (RO-RCOOR) radicals. Mono-esters of 2-hydroxycyclohexanone are preferred compounds and examples of such compounds are the acetate, butyrate, hexanoate, monoethyldiglycolate, monoethylthiodiglycolate, ethoxyacetate and monoethylphthalate of 2-hydroxycyclohexanone.

General methods of preparing esters of hydroxy-cyclohexanones have been heretofore described. The acetate of 2-hydroiwcyclohexanone was prepared heretofore by reacting 2-hydroxycyclohexanone with acetic anhydride, using pyridine as a solvent and by reacting 2-bromocyclohexanone with silver acetate. The benzoate of 2-hydroxycyclohexanone was prepared heretofore by esterifying 2-hydroxycyclohexanone with benzoyl chloride in pyridine in the presence of a trace of acetic acid as a catalyst, in one case, and in the absence of acetic acid in another; and, according to another method, by oxidizing mono-benzoyl cyclohexane-1,2-diol with potassium dichromate and sulfuric acid. None of these general methods are commercially feasible for the preparation of compounds which are to be used as camphor substitutes or to replace other plasticizers because the costs of the products made according to such methods are too high.

The foregoing heretofore known methods involve either the initial preparation of 2-hydroxycyclohexanone, which is not simple; theme of acid chlorides, which are expensive; the use of silver bromide, which is expensive and will be partially lost and unrecovered; or the use of oxidizing procedures which require a high degree of control to produce good yields. Because of these, and for other obvious reasons militating against the use of these general methods for the production of the compounds, I had considered using the reaction of chlorocyclohexanone or bromocyclohexanone with sodium acetate. The reaction of 2-chlorocyclohexanone and 2-bromocyclohexanone with sodium acetate in glacial acetic acid was heretofore described, however, but the only product which is formed is cyclohexenone, according to Kotz and Grethe, in Journal fiir praktische Chemie, 1909, vol. 80 (New Series), pages 491 and 493 (see also Beilstein, Handbuch der organischen Chemie," Berlin, 1932, vol. VII, pages and 51).

After unsuccessful attempts to find other methods of making esters of hydroxycyclohexanones, in a commercially feasible manner, I tried the reaction of 2-chlorocyclohexanone with anhydrous sodium acetate in glacial acetic acid,

. and found, contrary to expectations based on the reports of others, that the reaction yielded the acetate of hydroxycyclohexanone in good yield. This general reaction is the basis of my preferred method of making acid esters of hydroxycyclohexanones and is illustrated in the examples which follow:

Exmrrs I.Acetate of z-hydrorilcvcloheranone The starting material for this synthesis is 2-chlorocyclohexanone which can be prepared by the direct chlorination of cyclohexanone. The chlorination may be conducted in a diluent such as benzene and is preferably conducted in the presence of marble or a similar material which will absorb'or neutralize the hydrogen chloride formed in the reaction. To restrict the chlorination to a monochlorinated derivative, the cyclohexanone is underchlorinated, that is, the chlorination is conducted to an extent corresponding to the conversion of about 33% but less than about and preferably not more than 67% to the monochlorinated cyclohexanone. From such a reaction mixture the chlorocyclohexanone, having a boiling point of approximately to 108. C. at a pressure of 26 mm., can be separated by fractional distillation.

A mixture of 85 grams of anhydrous sodium acetate (about 1.04 mol) suspended in '70 grams of glacial acetic acid (about 1.17 mol) is placed in a flask provided with a stirrer and reflux condenser. The mixture is heated to about 100 C. and 125 grams of 2-chlorocyclohexanone (about 0.94 mol) is added thereto in small portions by means of a dropping funnel while a gentle reflux is maintained. The heating is continued at such a temperature as to maintain the gentle reflux for about 12 hours. The reaction mixture is then cooled and diluted with sufllcient water to dissolve the salts. Benzeneis then added to take up the organic substances and thereafter the aqueous and benzene layers are separated. The benzene layer is washed with water and then with dilute sodium carbonate solution and finally with water until the washings are approximately neutral. The benzene solution is then fractionated, the product being recovered in vacuum. The acetate oi 2-hydroxycyclohexanone has a boiling point of about 108 to 110 C. at a pressure of 10 mm., a boiling point of about 112 C. at 12 mm., and about 235 C. at atmospheric pressure. Its melting point is 40 to 42 C. The yield was 102 grams of ester, which is approximately 69% of the theoretical yield based on the 2-chlorocyclohexanone used in the reaction.

Instead of using pure 2-chlorocyclohexanone in the foregoing preparation, an underchlorinated cyclohexanone reaction mixture from which reacted and unreacted marble or other hydrogen-chloride-absorbent has been removed, may beused.

Examrs IL-Butyrate of Z-hydromycyclohexanone Into a three-neck flask, provided with a reflux condenser, stirrer and dropping funnel, is placed 148 grams of 99% butyric acid (about 1.66 mol). Sodium hydroxide pellets are then added slowly while the mixture is agitated, until 30.5 grams of sodium hydroxide (about 0.76 mol) has been added. The mixture is then heated while stirring until all the sodium hydroxide is dissolved and the water formed in the reaction is then distilled oil in partial vacuum, so as to leave anhydrous sodiumbutyrate-and butyric acid in the flask.

To the anhydrous sodium butyrate-butyric acid mixture (about 0.76 mol sodium 'butyrate and 0.89 mol butyric acid) thus obtained is then added slowly, through the dropping funnel, 84 grams of 2-chlorocyclohexanone (about 0.63 mol) while maintaining a reaction temperature ofabout 150 C. The reaction mixture is then maintained at a gentle reflux, the temperature being about 145 to 150 C., for a period of about hours.

The product is recovered as in Example 1. The benzene layer may be dried with calcium chloride, sodium sulfate or other drying agent, if desired, prior to distillation. The butyrate of 2- hydroxycyclohexanone has a boiling point of about 125 to 130 C. at a pressure of 8 mm. and a boiling point of about 260- C. at atmospheric pressure. The yield was approximately 101 grams, which is 86.5% of the theoretical yield from the 2-chlorocyclohexanone used.

EXAMPLE m.n-He.'canoate of Z-hydromycyclohexanone The hexanoic acid ester of 2-hydroxycyclohexanone is prepared by substituting 116 grams of nhexanoic acid (about 1 mol) for the loutyric acid, grams of sodium hydroxide pellets (about 0.5 mol) for the 80.5 grams of such pellets, and 66 grams of Z-chlorocyclohexanone (about 0.5 mol) for the 84 grams of this compound in Example II, and the procedure thereindescribed is followed. The refluxing temperature is about 155 EXAMPLE IV.--Ethylphthalyl ester of Z-hydroxycyclohexanone Into a flask provided with a stirrer, a reflux condenser, and a dropping tube, is charged 88.8 grams of phthalic anhydride (about 0.6 mol) and 142 grams of anhydrous ethyl alcohol (about 3.1 mols) The mixture is heated to reflux temperature (about 81 C.) while stirring, and is refluxed gently for about one-half hour at this small portions (about 10 minutes being required for the addition). After this addition the mixture is refluxed for about 25 hours.

From the reaction mixture the monoethyh phthalyl ester of Z-hydroxycyclohexanone may be recovered as follows: The excess alcohol is removed by evaporation in vacuum to a maximum temperature of 130 C. or thereabout at a pressure of 20 mm. The mixture is then cooled and washed with 250 cc. of warm water (60 to 70 C.) and is thereafter stirred into 250 cc. of water containing about 15 grams of sodium carbonate or more, if required to maintain the mixture al-.

kaline to phenolphthalein. The aqueous layer is separated and the oily layer is again washed several times with water, preferably by heating at 60 to 70 C. with water for periods of about 30 minutes for each washing. The washed oil is then distilled in steam until about 500 cc. of distillate is collected. The distillate may be washed andtreated with dilute alkaline solutions for further purification if desired. The oil is then cooled to 10 to 15 C. and the solid crystalline material removed and washed with cold water in a suction filter and thereafter dried by suction and air drying.

The yield of the monoethylphthalyl ester of 2-hydroxycyclohexanone, having a melting point of 66 to 66.5 C., is about 107.4 grams, which corresponds to 74.0% of the theoretical based on the 0.5 mol of chlorocyclohexanone used. On recrystallization from 50% ethyl 'alcohol, the purified product had a melting point of 67 to 675 C.

According to the general method of preparing esters of hydroxycyclohexanones illustrated in the foregoing examples,- the procedure consists essentially in reacting a chlorinated cyclohexanone or a chlorination mixture containing unreacted cyclohexanone with a sodium or potassium salt of the acid corresponding to the desired ester in the presence of the free acid, under substantially anhydrous conditions. Other alkalimetal salts of the acid may be used, if desired. Isomeric chlorocyclohexanones may be used to prepare the corresponding derivatives although the invention is specifically directed to the use of 2-chlorocyclohexanone, which is the principal product obtained on direct chlorination of cyclohexanone. Brominated or iodinated cyclohexanones may be used instead of the chlorinated derivatives, in which case the reaction is faster but not as well adapted to commercial utilization. Other conventional methods of purification may be used for recovery of the ester of the hydroxycyclohexanone as is obvious.

In my method of preparing esters of hydroxy cyclohexanones I use approximately stoichiometrical quantities of the alkali-metal salt of the acid and the halogenated cyclohexanone, although an excess of about 50% or somewhat more of the alkali-metal salt of the acid may be used to drive the reaction with the halogenated chlorocyclohexanone toward completion. However, I prefer to avoid the use of free acid, as in the preparation of the ethylphthalyl ester of hydroxycyclohexanone (Example IV), or use it only in an amount corresponding stoichiometrically to approximately not more than that of the alkali-metal salt. The reaction mixture is heated at reflux temperatures for periods of one hour or longer, generally from four to thirty hours, as shown in the examples; or if large batches or somewhat less reactive substances are used, the reaction period may be even longer than this.

The esters of hydroxycyclohexanones are powerful solvents and plasticizers for cellulose esters such as cellulose nitrate and acetate. In respect to their action on cellulose nitrate they resemble camphor very closely and as plasticizers for cellulose nitrate are superlative camphor substitutes posessing properties not possessed by camphor. In general, the plasticizers are compatible with plastic substances embodying a plurality of -0-0 linkages as typified by polyvinyl acetal resins and cellulose derivatives such as cellulose esters and ethers. Plastic compositions modified by these plasticizers are illustrated in my 00 pending application, Serial Number 342,443, filed June 26, 1940.

Inasmuch as the foregoing specification comprises preferred embodiments of the invention it is to be understood that these are merely illustrative and that modifications and variations may be made therein in accordance with the principles herein set forth without departing substantially from the invention which is defined and limited only by the appended claims.

1. The method of producing an organic ester of a hydroxycyclohexanone comprising reacting a halogenated cyclohexanone with an alkalimetal salt of an organic acid in the presence of the acid under substantially anhydrous conditions.

2. The method of producing an organic ester of 2-hydroxycyclohexanone comprising reacting 2-chlorocyclohexanone with a sodium salt of an acid in the presence of the acid under substantially anhydrous conditions.

3. The method of producing the acetate of 2-hydroxycyclohexanone comprising heating together a reaction mixture comprising 2-chlorocyclohexanone, sodium acetate and acetic acid under substantially anhydrous conditions and recovering therefrom the acetate of z-hydroxycyclohexanone.

4. The method of producing the butyrate of Z-hydroxycyclohexanone comprising heating together a reaction mixture comprising 2-chlorocyclohexanone, sodium butyrate and butyric acid under substantially anhydrous conditions and recovering therefrom the butyrate of Z-hydroxycyclohexanone.

5. The method of producing the monoethylphthalyl ester of 2-hydroxycyclohexanone comprising heating together a reaction mixture comprising 2-chlorocyclohexanone and potassium monoethylphthalate under substantially anhydrous conditions and recovering therefrom the monoethylphthalyl ester of Z-hydroxycyclohexanone.

6. The method of producing an organic ester of a hydroxycyclohexanone comprising reacting a halogenated cyclohexanone with an alkali-metal salt of an organic acid under substantially anhydrous conditions.

7. The method of producing the acetate of 2-hydroxycyclohexanone which comprises heating at reflux temperature a mixture consisting essentially of anhydrous sodium acetate and glacial acetic acid while gradually adding 2-chlorocyclohexanone thereto in an amount less than that required stoichlometrically to convert all the sodium acetate to the acetate of 2-hydroxycyclohexanone, continuing the heating at reflux temperature after the addition of the chlorocyclohexanone to complete the predominant portion of the conversion and thereafter recovering the acetate of 2-hydroxycyclohexanone from the reaction mixture,

8. The method of producing the butyrate of 2-hydroxycyclohexanone which comprises heating at reflux temperature a mixture consisting essentially of sodium butyrate and butyric acid while gradually adding 2-chlorocyclohexanone thereto in an amount less than that required stolchiometrically to convert all the sodium butyrate to the butyrate of Z-hydroxycyclohexanone, continuing the heating at reflux temperature after the addition of the chlorocyclohexanone to complete the predominant portion of the conversion and thereafter recovering the butyrate of Z-hydroxycyclohexanone from the reaction mixture.

9. The method of producing the monoethylphthalyl ester of z-hydroxycyclohexanone which comprises heating at reflux temperature a mixture consisting essentially of the potassium salt of monoethylphthalic acid while gradually adding 2-chlorocyclohexanone thereto in an amount equivalent approximately to that required stoichiometrically to convert all the potassium salt of monoethylphthalic acid to the monoethylphthalyl ester of Z-hydroxycyclohexanone, continuing the heating at reflux temperature after the addition of the chlorocyclohexanone to complete the predominant portion of the conversion and thereafter recovering the monoethylphthalyl ester of 2-hydroxycyclohexanone from the reaction mixture.

10. A monoalkylphthalyl ester of 2-hydroxycyclohexanone.

11. The monoethylphthalyl ester of 2-hydroxycyclohexanone.

LUCAS P. KYRIDES.

CERTIFICATE OF CORRECTION. 7

Patent No. 2, 551,529 October 1 2,. 1915,

. LUCAS P. KYRIDES.

It is hereby'oertified that error'appears 1n the printed specification of the above numbered patent requiring correction as follows: Page 1 first column, .line 2h,--claim2,.af-ter the word Fan insert "organic-e, and that the seid Letters Patent should be read with this correction therein that the same may conform' to' the record of-the case in the Patent Office.

Signed and sealed this hm dayof January, A, D. 19%.

, Henry Van Arsdale,

(Seal) Acting Commissioner of Patents. 

